In other species: wild cat , lion , jaguar , leopard , tiger , puma , Eurasian lynx , snow leopard , cheetah , ocelot , little spotted cat , jungle cat , sand cat , black-footed cat , margay , Canada lynx , bobcat , rusty-spotted cat , fishing cat , caracal , serval , Colocolo , Pallas's cat , African golden cat , Clouded leopard , Asiatic golden cat , Spanish lynx , jaguarundi

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 603209 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Disease-related: no

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: Each blood group system consists of a set of blood types, each of which corresponds to a particular antigen (usually a glycoprotein) on the surface of red blood cells. The different types within a system are the result of the action of different alleles at a locus that usually encodes an enzyme that catalyses the creation of the feature of the glycoprotein unique to that type, e.g. the presence of a particular sugar at the end of a short chain of sugars.

Species-specific description: As summarised by Kehl et al. (2019): "The feline AB blood group system is composed of type A, B and C (also called AB). It is of great clinical importance, as blood incompatibilities can result in acute hemolytic transfusion reactions and hemolysis of the newborn [neonatal isoerythrolysis (NI)] due to presence of naturally occurring anti-A alloantibodies (Auer & Bell 1981; Auer et al. 1982; Giger et al. 1991; Giger 2014). The enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH; EC1.14.18.2) converts sialic acid N-acetylneuraminic acid (NeuAc; type B antigen) to N-glycolylneuraminic acid (NeuGc; type A antigen)." Ginoudis et al. (2024) "report of a cat without appreciable A or B antigen on erythrocytes assessed by an in-clinic typing kit. The cat ... was confirmed as of bb genotype, bearing the CMAH variant c.179G>T, which results in blood type B. These studies suggest an unusual weak type B or missing all ABC antigens."

History: As noted by Bighignoli et al. (2007), "CMAH represents the first blood group gene identified outside of non-human primates and humans".

Inheritance: As summarised by Kehl et al. (2019): "The CMAH locus is proposed to have three alleles with several haplotypes in the allelic series of A>a^c>b (Giger et al. 1991; Griot-Wenk & Giger 1995). Thus, genotypes A/A, A/b and A/a^c can be observed in type A cats, b/b in type B and a^c/a^c and a^c/b in type C cats."

Molecular basis: Bighignoli et al. (2007) reported haplotypes within the CMAH gene that correspond with the A and b alleles of this blood group system. The haplotypes are characterised by six mutations: "2 SNPs upstream of the start, an indel in the exon 1 5' UTR and three missense mutations in the coding region". Gandolfi et al. (2016): "A novel variant [in CMAH], c.364C>T, was identified that is highly associated with blood type AB in Ragdoll cats and, to a lesser degree, with type AB in random bred cats". The study identified an additional missense variant (c.327A>C, unique to a blood type B random bred cat) and three silent variants (c.1158T>C, c.1269A>G, c.1398G>T). Two new variants (c.179G>T and c.187A>G) were reported by Omi et al. (2016). Omi et al. (2016) also genotyped the c.327A>C identified by Gandolfi et al. (2016) and concluded that this "mutation alone does not determine type AB cats but might be highly associated with the expression of Neu5Ac in these cats." Kehl et al. (2018) describe 8 additional variants (c.374C>T, c.376G>A, c.593A>C, c.868A>C, c.898A>G, c.933delA, c.1322delT, c.1342G>A). Uno et al. (2021) "describe the detection of an incompatible cross-match case (subject K) in the feline AB blood group system, and another cat (subject R) with discordant results from the card agglutination (CARD) method and alloantibody agglutination test for blood typing. We here describe our results from serological and genetic investigations to characterize blood samples from these two cats. We then characterized the low-frequency haplotypes carried according to six mutations and a novel haplotype with a new SNP [c.773G>A] in the feline CMAH genes of these cats."

Prevalence: Gavazza et al. (2021) performed a systematic review of "27 articles on the prevalence of cat blood groups .... . For each scientific study, we obtained the prevalence of the blood group divided into A, B, AB, and Mik. The means of the prevalence rates for each blood group showed that group A was high in all cats, 86% in Asian breeds, 84% in American breeds, 76%in European breeds, and 72% in breeds from Oceania), while group B prevalence was higher in European and Oceanian breeds (respectively, 21% and 27%) compared with Asian and American breeds (8% and 8%, respectively). The means of the prevalence rate of group AB was lower in all cats (6% in Asian breeds, 8% in American breeds, 3% in European breeds, and 1% in the breed from Oceania)."

Genetic testing: Kehl et al. (2018) proposed a revised variant panel for the genotypic determination of blood group phenotype (A, B, or C (=AB)). The panel comprises four variants: c.179G>T, c.268T>A, c.364C>T, and c.1322delT, which, as shown in Table 1 of Kehl et al. (2019) enable the determination of all relevant genotypes and hence phenotypes across a wide range of breeds. These variants are labelled "2019 TYPING PANEL" in the variant table below.

Associated gene: